Hybrid tumor cells are a unique means to induce specific antitumor immunity. The hybrids are produced by obtaining cells from a patient's tumor as the first parent, and cells which grow readily in culture as the second parent, and exposing both to a fusogen. The resulting hybrids have the following advantages: (1)\they can be grown in culture to produce unlimited quantities; (2)\they express on their cell surfaces the required immunizing tumor-associated antigens (empirical evidence) and can effectively serve as antitumor immunogens; and (3)\the character of the hybrid cell surface is partly "selectable" by virtue of our freedom to choose the second parent cell. In our view, the experimental knowledge most needed to advance the hybrid immunization concept is: (1)\to identify those methods which consistently yield tumor cell hybrids of high immunogenicity; and (2)\to determine by human trial the safety, immunological effects and therapeutic value of this concept. We plan, in this research, to do the following: (1)\to test in animals the hypothesis that the mutant cell line selected as the second parent for fusion is a major determinant of hybrid immunogenicity; (2)\to assess the value of tumor cell skin testing and autologous lymphocyte cytotoxicity as ways to determine the adequacy of immunization and strength of specific immunity; (3)\to evaluate with human hybrids the problem of chance fusion with the nonmalignant cells of solid tumors and develop methods to select only those clones derived from malignant cells; and (4)\to conduct a human trial of hybrid tumor cell immunization for patients with malignant melanoma or renal carcinoma. The procedures require extensive use of cell fusion techniques and DNA analyses of hybrids by flow cytometry. The concepts involved will be tested in two animal tumor models. Genetic markers will be placed in human cell lines to prepare double mutants suitable for fusion. If this immunologic approach to therapy is safe and able to induce remissions, it is adaptable for use against all types of cancer.